DE69940602D1 - CELLS AND ANIMALS WITH DEFICIT TO PROTEIN KINASE C EPSILON - Google Patents

CELLS AND ANIMALS WITH DEFICIT TO PROTEIN KINASE C EPSILON

Info

Publication number
DE69940602D1
DE69940602D1 DE69940602T DE69940602T DE69940602D1 DE 69940602 D1 DE69940602 D1 DE 69940602D1 DE 69940602 T DE69940602 T DE 69940602T DE 69940602 T DE69940602 T DE 69940602T DE 69940602 D1 DE69940602 D1 DE 69940602D1
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DE
Germany
Prior art keywords
pkcepsilon
drugs
present
epsilon
inhibitors
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
DE69940602T
Other languages
German (de)
Inventor
Robert O Messing
Clyde W Hodge
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
University of California
Original Assignee
University of California
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Filing date
Publication date
Application filed by University of California filed Critical University of California
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Publication of DE69940602D1 publication Critical patent/DE69940602D1/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0276—Knock-out vertebrates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A61K31/515—Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/005—Enzyme inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/36—Opioid-abuse
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0356—Animal model for processes and diseases of the central nervous system, e.g. stress, learning, schizophrenia, pain, epilepsy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Genetics & Genomics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Biotechnology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • General Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biochemistry (AREA)
  • Neurology (AREA)
  • Microbiology (AREA)
  • Neurosurgery (AREA)
  • Addiction (AREA)
  • Environmental Sciences (AREA)
  • Psychiatry (AREA)
  • Plant Pathology (AREA)
  • Pain & Pain Management (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Animal Husbandry (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)

Abstract

The present invention is directed to the production of PKC isozyme epsilon (PKCepsilon)-deficient cells and non-human animals. The present invention is further directed to the identification of PKCepsilon as a target for drugs that reduce anxiety. According to the present invention, PKCepsilon-inhibiting compounds act in synergy with drugs acting at the GABAA receptor. The present invention is also directed to the use of modulators of PKCepsilon to modulate alcohol consumption, self-administration of other drugs of abuse, and the effects of alcohol consumption as well as the use of inhibitors of PKCepsilon, either alone or in conjunction with allosteric agonists of GABAA receptors, to treat conditions, such as addiction, withdrawal syndrome, skeletal muscle spasms, convulsive seizures, and epilepsy, that are amenable to treatment by allosteric agonists of GABAA receptors. Additional aspects of the present invention are diagnostic methods for identifying individuals at risk for becoming alcoholics or abusers of other drugs and kits for performing such diagnostic methods. The present invention relates to: cells and non-human animals deficient for the PKC isozyme epsilon (PKCepsilon); the use of PKCepsilon as a target for drugs; the use of inhibitors of PKCepsilon in methods of reducing anxiety and treating conditions associated with insufficient activity of the GABAA receptor; the use of modulators of PKCepsilon in methods of modulating alcohol consumption, modulating self-administration of other drugs of abuse, and altering the effects of alcohol; pharmaceutical compositions comprising inhibitors of PKCepsilon and allosteric agonists of GABAA receptors; and the identification of individuals with enhanced susceptibility to alcoholism or other forms of addiction.
DE69940602T 1998-07-06 1999-07-02 CELLS AND ANIMALS WITH DEFICIT TO PROTEIN KINASE C EPSILON Expired - Lifetime DE69940602D1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US9175598P 1998-07-06 1998-07-06
US12599599P 1999-03-24 1999-03-24
US09/340,283 US6717030B2 (en) 1998-07-06 1999-06-25 Protein kinase C epsilon as modulator of anxiety, alcohol consumption and self-administration of drugs of abuse
PCT/US1999/015152 WO2000001805A1 (en) 1998-07-06 1999-07-02 Cells and animals deficient in protein kinase c epsilon

Publications (1)

Publication Number Publication Date
DE69940602D1 true DE69940602D1 (en) 2009-04-30

Family

ID=27376970

Family Applications (1)

Application Number Title Priority Date Filing Date
DE69940602T Expired - Lifetime DE69940602D1 (en) 1998-07-06 1999-07-02 CELLS AND ANIMALS WITH DEFICIT TO PROTEIN KINASE C EPSILON

Country Status (10)

Country Link
US (4) US6717030B2 (en)
EP (1) EP1095136B1 (en)
JP (3) JP2002522012A (en)
AT (1) ATE426019T1 (en)
AU (1) AU768569B2 (en)
CA (1) CA2332488C (en)
DE (1) DE69940602D1 (en)
IL (1) IL140651A0 (en)
NZ (1) NZ508946A (en)
WO (1) WO2000001805A1 (en)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6717030B2 (en) * 1998-07-06 2004-04-06 The Regents Of The University Of California Protein kinase C epsilon as modulator of anxiety, alcohol consumption and self-administration of drugs of abuse
DE10141650C1 (en) 2001-08-24 2002-11-28 Lohmann Therapie Syst Lts Safe transdermal therapeutic system for administration of fentanyl or analogous analgesics, having matrix layer of carboxy group-free polyacrylate adhesive providing high permeation rate
US6933275B2 (en) * 2002-05-01 2005-08-23 The Board Of Trustees Of The Leland Stanford Junior University Protein kinase C peptides for use in withdrawal
JP4675109B2 (en) * 2003-05-16 2011-04-20 ザ ボード オブ トラスティーズ オブ ザ レランド スタンフォード ジュニア ユニバーシティー Protein kinase C peptide for use in withdrawal symptoms
US8598146B2 (en) 2003-09-16 2013-12-03 Garvan Institute Of Medical Research Methods for identifying modulators of protein kinase C-epsilon (PKCε) and method of treatment of aberrant glucose metabolism associated therewith
US20050070565A1 (en) * 2003-09-26 2005-03-31 Arnsten Amy F.T. Chelerythrine, analogs thereof and their use in the treatment of bipolar disorder and other cognitive disorders
AU2003264918A1 (en) * 2003-10-02 2005-04-21 The Board Of Trustees Of The Leland Stanford Junior University Protein kinase c peptides for use in withdrawal
GB0325130D0 (en) * 2003-10-28 2003-12-03 Smith & Nephew Apparatus with scaffold
GB0424046D0 (en) * 2004-10-29 2004-12-01 Smith & Nephew Apparatus
US8529548B2 (en) * 2004-04-27 2013-09-10 Smith & Nephew Plc Wound treatment apparatus and method
WO2006075187A2 (en) * 2005-01-14 2006-07-20 Medical Research Council Animals exhibiting an altered preference for an addictive substance
EP1896496B1 (en) * 2005-06-29 2012-01-11 Hadasit Medical Research Services & Development Ltd. Protein kinase c inhibitors for prevention of insulin resistance and type 2 diabetes
US7951232B2 (en) * 2006-02-09 2011-05-31 Elevance Renewable Sciences, Inc. Surface coating compositions and methods
MX2008010359A (en) * 2006-02-09 2009-01-30 Elevance Renewable Sciences Antimicrobial compositions, methods and systems.
US8338402B2 (en) * 2006-05-12 2012-12-25 Smith & Nephew Plc Scaffold
JP2010090176A (en) * 2010-01-26 2010-04-22 Board Of Trustees Of The Leland Stanford Junior Univ Protein kinase c peptide for use in withdrawal symptom
US8785648B1 (en) 2010-08-10 2014-07-22 The Regents Of The University Of California PKC-epsilon inhibitors
WO2016003450A1 (en) 2014-07-01 2016-01-07 The Regents Of The University Of California Pkc-epsilon inhibitors

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US5464764A (en) * 1989-08-22 1995-11-07 University Of Utah Research Foundation Positive-negative selection methods and vectors
AU637014B2 (en) * 1990-11-02 1993-05-13 Sphinx Pharmaceuticals Corporation Bis-(hydroxyalkylamino)-anthraquinone inhibitors of protein kinase c
US5141957A (en) * 1990-11-02 1992-08-25 Sphinx Pharmaceuticals Corporation 1,4-bis-(amino-hydroxyalkylamino)-anthraquinones for inhibiting protein kinase c
US5216014A (en) * 1991-09-10 1993-06-01 Sphinx Pharmaceuticals Corporation Furo-coumarinsulfonamides as protein kinase C inhibitors
US5360818A (en) * 1991-09-23 1994-11-01 Sphinx Pharmaceuticals Corporation 1,3-dioxane derivatives having protein kinase C inhibitory activity
US5270310A (en) * 1991-12-13 1993-12-14 Sphinx Pharmaceuticals Corporation N-aminoalkyl amide inhibitors of protein kinase C
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US5935803A (en) * 1994-02-01 1999-08-10 Terrapin Technologies, Inc. Methods to identify immunomodulators using cognate interaction of PKC-theta
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WO1998017299A1 (en) * 1996-10-18 1998-04-30 The Board Of Trustees Of The Leland Stanford Junior University Isozyme-specific activators of protein kinase c, methods and compositions
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US6717030B2 (en) * 1998-07-06 2004-04-06 The Regents Of The University Of California Protein kinase C epsilon as modulator of anxiety, alcohol consumption and self-administration of drugs of abuse

Also Published As

Publication number Publication date
US20020124272A1 (en) 2002-09-05
JP2002522012A (en) 2002-07-23
CA2332488C (en) 2010-03-23
AU768569B2 (en) 2003-12-18
JP2009084291A (en) 2009-04-23
CA2332488A1 (en) 2000-01-13
EP1095136A1 (en) 2001-05-02
US20070039063A1 (en) 2007-02-15
US20040191898A1 (en) 2004-09-30
NZ508946A (en) 2003-11-28
US20070039064A1 (en) 2007-02-15
US7534859B2 (en) 2009-05-19
EP1095136B1 (en) 2009-03-18
AU4968999A (en) 2000-01-24
JP2008220373A (en) 2008-09-25
ATE426019T1 (en) 2009-04-15
WO2000001805A1 (en) 2000-01-13
US6717030B2 (en) 2004-04-06
IL140651A0 (en) 2002-02-10

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